This proposal describes our proposed studies for the continuation of the Soft Tissue Sarcoma (STS) Project, CA 47179. We have continued the overall original objectives of implementing a comprehensive and integrated multidisciplinary program approach toa the biology, pathogenesis, and natural history of soft tissue sarcoma in order to translate this information into improved treatment of STS. Thus, our research program on the biology of STS and our pharmacology program investigating mechanisms of drug resistance are geared to the development of novel therapeutic agents and strategies. A major resource of this program is the patient population; over the 12 years, 2599 adult patients with STS have been admitted to MSKCC. We continue to maintain a comprehensive prospective database on this population. In the revised renewal application, we have maintained our current projects designed to explore new directions based on our experience over the past several years. In Casper's project, Clinical Studies, with new co-project leaders we have refined our efforts to develop a dose intensification program using isolated lung perfusion as well as to redirect our immunotherapy program to develop a tumor vaccine program. Both clinical trials, and preclinical studies are incorporated into this project. In Cordon-Cardo's Project, based on our previous studies, we have focussed our efforts of an investigation of mutations and altered patterns of TP53 and retinoblastoma (RB) genes and their relationships to tumor growth and metastasis. The ultimate goal of these is the identification of new therapeutic targets in the design of clinical trials. In Bertino's Project studies are planned on the biochemical and molecular characterization of drug resistance. This information is important for the development of rational strategies for the therapeutic use of novel chemotherapeutic regimens. The interaction between RB expression and drug resistance interrelates project 3. The research projects are supported by 3 cores: Administrative/Clinical, Pathology and Biostatistics.